Molecular mimicry is a model of autoimmunity in which an immune response mounted against a specific antigenic determinant of an infectious/foreign agent cross-reacts with a "mimicked" host sequence, leading to autoimmunity and tissue injury. Type-C retroviruses have been associated with autoimmune connective tissue disorders (ACTD) in both humans and animals. Recent work in this laboratory showed an area of immunologic cross-reactivity between a major target of human autoimmunity, the 70 kilodalton U1 snRNP-associated protein (70K), and p30gag protein of type C retroviruses. We will further investigate the significance of this cross-reactivity, and determine whether p30gag cross-reactivity with 70K protein plays a role in initiating autoimmunity in humans and animals. Specifically, we will use immunofluorescence and immunoblotting techniques to characterize a p30gag-like antigen which has been repeatedly identified in glomerular immune complex deposits from patients with systemic lupus erythematosus. We will utilize autoimmune mouse strains to further investigate the significance of the cross-reactivity of p30gag and 70K protein. By analyzing the development of antibodies to specific epitopes on the mouse 70K protein, we hope to demonstrate that host recognition of the region of cross-reactivity on the 70K protein is followed by expanding autoimmunity to surrounding epitopes. We will then test the ability of p30gag protein to induce an autoimmune response in non-autoimmune mouse strains through the use of immunizations and the construction of transgenic mice. Another goal of these experiments is to identify expressed human p30gag proteins by identifying their corresponding cDNAs. This will be complemented by characterization of the gene(s) coding for human p30gag and by investigation of the expression of this gene(s) in human autoimmune disease.